Human milk is known to contain a large amount of indigestible oligosaccharides. In fact, indigestible oligosaccharides represent the third largest solid component (after lactose and lipids) in breast milk, occurring at a concentration of 12-15 g/l in colostrum and 5-8 g/l in mature milk. Human milk oligosaccharides are very resistant to enzymatic hydrolysis, indicating that these oligosaccharides may display essential functions not directly related to their calorific value.
Over the past two decades, the chemical structures of human milk oligosaccharides have been studied using NMR spectroscopy and mass spectrometry. Each individual oligosaccharide is based on a combination of glucose, galactose, sialic acid (N-acetylneuraminic acid), fucose and/or N-acetylglucosamine with many and varied linkages between them, thus accounting for the enormous number of different oligosaccharides in human milk—over 130 such structures have been identified so far. Almost all of them have a lactose moiety at their reducing end while sialic acid (when present) occupies the terminal position at the non-reducing end.
The large quantity of sialylated oligosaccharides in human milk is of particular interest. Sialic acid is a nine-C sugar that is a vital structural and functional component of brain gangliosides. It is thought to play an essential role in nerve cell transmission, memory formation and cell to cell communication. Studies in rat pups indicate that early supplementation with sialic acid improves both brain ganglioside sialic acid and learning ability in well-nourished and malnourished animals and that these changes persist into adulthood.
Mother's milk is recommended for all infants. However, in some cases breast feeding is inadequate or unsuccessful for medical reasons or the mother chooses not to breast feed. Infant formulas have been developed for these situations. However, bovine milk which is usually used as the basis of commercially available infant formulas has a much lower content of sialylated oligosaccharides than human milk. As the structure of human milk and the functions of the individual components thereof becomes better understood, it has become apparent that it may be desirable to improve the sialic acid content of infant formulas based on bovine milk.
There are several known sources of sialic acid including free N-acetylneuraminic acid, sialyllactose and other sialylated oligosaccharides, sialic-acid containing gangliosides, and the peptide caseinoglycomacropeptide. Caseinoglycomacropeptide or CGMP is a large carbohydrate-rich, hydrophilic peptide which is the C-terminal moiety of κ casein from which it may be cleaved by enzymatic or acid treatment. In United States Patent Application No. 2005/0096295 it is proposed to increase the sialic acid content of infant formula by including a novel CGMP ingredient having an enhanced concentration of sialic acid. This ingredient has a sialic acid content of more than 60 mg/g of peptide compared with 40 to 60 mg/g of peptide in naturally occurring CGMP. It may be produced either by fractionation using anion chromatography or by partial hydrolysis followed by fractionation using anion chromatography.
However, a need remains to provide other ingredients rich in sialic acid which can be used to enrich infant formula and other nutritional compositions in this important component.